Expandable Stimulation Electrode with Integrated Pressure Sensor and Methods Related Thereto

ABSTRACT

An apparatus is provided having at least one fixation electrode adapted to abut a wall of a pulmonary artery, and a pressure sensor integrally supported by the at least one fixation electrode. The pressure sensor provides a signal indicative of a blood pressure in the pulmonary artery. The apparatus also includes a pulse generator coupled with the at least one fixation electrode, the pulse generator adapted to deliver a baroreflex stimulation signal to one or more baroreceptors in the pulmonary artery via the at least one fixation electrode. The pressure sensor is anchorable in the pulmonary artery via the at least one fixation electrode.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/284,063, filed on Oct. 29, 2002, which is a continuation-in-part ofU.S. patent application Ser. No. 09/671,850 filed on Sep. 27, 2000,which is now issued as U.S. Pat. No. 6,522,926, the full disclosures ofwhich are incorporated herein by reference. The parent application forthis application has incorporated by reference the disclosures of thefollowing U.S. Patent Applications: U.S. patent application Ser. No.09/964,079, filed on Sep. 26, 2001, now issued as U.S. Pat. No.6,985,774, U.S. patent application Ser. No. 09/963,777, filed Sep. 26,2001, and U.S. patent application Ser. No. 09/963,991, filed on Sep. 26,2001, now issued as U.S. Pat. No. 6,850,801, now issued as U.S. Pat. No.6,850,801, the disclosures of which are also effectively incorporated byreference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention generally relates to medical devices and methodsof use for the treatment and/or management of cardiovascular, renal, andneurological disorders. Specifically, the present invention relates todevices and methods for controlling the low-pressure baroreflex systemfor the treatment and/or management of cardiovascular, renal, andneurological disorders.

Cardiovascular disease is a major contributor to patient illness andmortality. It also is a primary driver of health care expenditure,costing more than $326 billion each year in the United States.Hypertension, or high blood pressure, is a major cardiovascular disorderthat is estimated to affect over 50 million people in the United Satesalone. Hypertension occurs when the body's smaller blood vessels(arterioles) constrict, causing an increase in blood pressure. Becausethe blood vessels constrict, the heart must work harder to maintainblood flow at the higher pressures. Although the body may tolerate shortperiods of increased blood pressure, sustained hypertension mayeventually result in damage to multiple body organs, including thekidneys, brain, eyes and other tissues, causing a variety of maladiesassociated therewith.

Heart failure is the final common expression of a variety ofcardiovascular disorders, including ischemic heart disease. It ischaracterized by an inability of the heart to pump enough blood to meetthe body's needs and results in fatigue, reduced exercise capacity andpoor survival. It is estimated that approximately 5,000,000 people inthe United States suffer from heart failure, directly leading to 39,000deaths per year and contributing to another 225,000 deaths per year.Heart failure results in the activation of a number of body systems tocompensate for the heart's inability to pump sufficient blood. Many ofthese responses are mediated by an increase in the level of activationof the sympathetic nervous system, as well as by activation of multipleother neurohormonal responses. Generally speaking, this sympatheticnervous system activation signals the heart to increase heart rate andforce of contraction to increase the cardiac output; it signals thekidneys to expand the blood volume by retaining sodium and water; and itsignals the arterioles to constrict to elevate the blood pressure. Thecardiac, renal and vascular responses increase the workload of theheart, further accelerating myocardial damage and exacerbating the heartfailure state. Accordingly, it is desirable to reduce the level ofsympathetic nervous system activation in order to stop or at leastminimize this vicious cycle and thereby treat or manage the heartfailure.

A number of drug treatments have been proposed for the management ofhypertension, heart failure and other cardiovascular disorders. Theseinclude vasodilators to reduce the blood pressure and ease the workloadof the heart, diuretics to reduce fluid overload, inhibitors andblocking agents of the body's neurohormonal responses, and othermedicaments. Various surgical procedures have also been proposed forthese maladies. For example, heart transplantation has been proposed forpatients who suffer from severe, refractory heart failure.Alternatively, an implantable medical device such as a ventricularassist device (VAD) may be implanted in the chest to increase thepumping action of the heart. Alternatively, an intra-aortic balloon pump(IABP) may be used for maintaining heart function for short periods oftime, but typically no longer than one month. Other surgical proceduresare available as well. No one drug, surgical procedure, or assistsystem, however, has provided a complete solution to the problems ofhypertension and heart failure.

For these reasons, it would be desirable to provide alternative andimproved methods for treating hypertension, heart failure, and othercardiovascular, neurological, and renal disorders. Such methods andsystems should allow for treatment of patients where other therapieshave failed or are unavailable, such as heart transplantation. It wouldbe further desirable if the methods could lessen or eliminate the needfor chronic drug use in at least some patients. Additionally, it wouldbe desirable if the methods and systems were mechanically simple andinherently reliable, in contrast to complex mechanical systems such asVAD's, IABP's, and the like.

One particularly promising approach for improving the treatment ofhypertension, heart failure, and other cardiovascular and renaldisorders is described in published PCT Application No. WO 02/026314,which claims the benefit of U.S. patent application Ser. No. 09/671,850,which is the parent of the present application. The full disclosures ofboth WO 02/026314 and U.S. Ser. No. 09/671,850, are incorporated hereinby reference. WO 02/026314 describes the direct activation ofbaroreceptors for inducing changes in a patient's baroreflex system tocontrol blood pressure and other patient functions. The priorapplications are particularly directed at the activation of thebaroreceptors present in the carotid sinus and the aortic arch. Both thecarotid sinus and aortic arch are on the high-pressure or arterial sideof the patient's vasculature. They are referred to as high-pressuresince pressures in the systemic arterial circulation are higher thanthose in the veins and pulmonary circulation. Activation of thehigh-pressure baroreceptors can send signals to the brain that causereflex alterations in nervous system function which result in changes inactivity of target organs, including the heart, vasculature, kidneys,and the like, typically to maintain homeostasis.

While highly promising, the need to implant electrodes or othereffectors on the arterial or high-pressure side of the vasculature maybe disadvantageous in some respects. Arteries and other vessels on thehigh-pressure side of the vasculature are at risk of damage, andimplantation of an electrode on or in the carotid sinus or aortic archrequires more care, and improper device implantation on the arterialside presents a small risk of arterial thromboembolism which in turn cancause stroke and other organ damage. Some arterial locations can alsocause unwanted tissue or nerve stimulation due to current leakage.

Thus, it would be desirable to provide improved methods and systems forartificial and selective activation of a patient's baroreflex system inorder to achieve a variety of therapeutic objectives, including thecontrol of hypertension, renal function, heart failure, and thetreatment of other cardiovascular. and neurological disorders. It wouldbe particularly desirable if such methods and systems did not requireintervention on the arterial or high-pressure side of a patient'svasculature, thus lessening the risk to the patient of arterial damageand damage resulting from thromboembolism or hemorrhage. At least someof these objectives will be met by the inventions described hereinafter.

2. Description of the Background Art

U.S. Pat. Nos. 6,073,048 and 6,178,349, each having a common inventionwith the present application, describe the stimulation of nerves toregulate the heart, vasculature, and other body systems. Nervestimulation for other purposes is described in, for example, U.S. Pat.No. 6,292,695 B1 and U.S. Pat. No. 5,700,282. Publications describingbaropacing of the carotid arteries for controlling hypertension includeNeufeld et al. (1965) Israel J. Med. Sci 1:630-632; Bilgutay et al.,Proc. Baroreceptors and Hypertension, Dayton, Ohio, Nov. 16-17, 1965, pp425-437; Bilgutary and Lillehei (1966) Am. J. Cariol. 17:663 -667; andItoh (1972) Jap. Heart J. 13: 136-149. Publications which describe theexistence of baroreceptors and/or related receptors in the venousvasculature and atria include Goldberger et al. (1999) J. Neuro. Meth.91:109-114; Kostreva and Pontus (1993) Am. J. Physiol. 265:G15-G20;Coleridge et al. (1973) Circ. Res. 23:87-97; Mifflin and Kunze (1982)Circ. Res. 51:241-249; and Schaurte et al. (2000) J. CardiovascElectrophysiol. 11:64-69.

BRIEF SUMMARY OF THE INVENTION

To address hypertension, heart failure, cardia arrhythmias, andassociated cardiovascular, renal, and nervous system disorders, thepresent invention provides a number of devices, systems and methods bywhich the blood pressure, nervous system activity, and neurohormonalactivity may be selectively and controllably regulated by activatingbaroreceptors. By selectively and controllably activating baroreceptors,the present invention reduces excessive blood pressure, sympatheticnervous system activation and neurohormonal activation, therebyminimizing their deleterious effects on the heart, vasculature and otherorgans and tissues.

In an exemplary embodiment, the present invention provides a system andmethod for treating a patient by inducing a baroreceptor signal toeffect a change in the baroreflex system (e.g., reduced heart rate,reduced blood pressure, etc.). The baroreceptor signal is activated orotherwise modified by selectively activating baroreceptors. Toaccomplish this, the system and method of the present invention utilizea baroreceptor activation device positioned near a baroreceptor in thevenous or low-pressure side of a patient's vasculature. As usedhereinafter, the phrase “low-pressure side of the vasculature” will meanthe venous and cardiopulmonary vasculature, including particularly thechambers in the heart, veins near the entrances to the atria, thepulmonary artery, the portal vein of the liver, the superior vena cava(SVC), the inferior vena cava (IVC), the jugular vein, the subclavianveins, the iliac veins, the femoral veins, and other peripheral areas ofthe vasculature where baroreceptor and baroreceptor-like receptors arefound. Particular target mechanoreceptors are described in Kostreva andPontus (1993), cited above, the full disclosure of which is incorporatedherein by reference.

The baroreceptors and baroreceptor-like receptors on the low-pressureside of the vasculature will function similarly to, but not necessarilyidentically to, baroreceptors on the high-pressure side of thevasculature. In general, cardiovascular receptors may be sensitive topressure and/or mechanical deformation and are referred to asbaroreceptors, mechanoreceptors, pressoreceptors, stretch receptors, andthe like. For cardiovascular and renal therapies, the present inventionis intended to activate or otherwise interact with any or all of thesetypes of receptors so long as such activation or interaction results inmodulation of the reflex control of the patient's circulation. Whilethere may be small structural or anatomical differences among variousreceptors in the vasculature, for the purposes of the present invention,activation may be directed at any of these receptors so long as theyprovide the desired effects. In particular, such receptors will provideafferent signals, i.e., signals to the brain, which provide the bloodpressure and/or volume information to the brain which allow the brain tocause “reflex” changes in the autonomic nervous system which in turnmodulate organ activity to maintain desired hemodynamics and organperfusion. Such activation of afferent pathways may also affect brainfunctions in such a way that could aid in the treatment of neurologicdisease.

The ability to control the baroreflex response and cardiovascular,renal, and neurological function, by intervention on the low-pressureside of the vasculature is advantageous in several respects.Intervention on the venous and cardiopulmonary side of the vasculaturereduces the risk of organ damage, including stroke, from systemicarterial thromboembolism. Moreover, the devices and structures used forintervening on the venous and cardiopulmonary side of the vasculaturemay be less complicated since the risk they pose to venous circulationis much less than to arterial circulation. Additionally, theavailability of venous and cardiopulmonary baroreceptors allowsplacement of electrodes and other devices which reduce the risk ofunwanted tissue stimulation resulting from current leakage to closelyadjacent nerves, muscles, and other tissues.

Generally speaking, the baroreceptor activation device may be activated,deactivated or otherwise modulated to activate one or more baroreceptorsand induce a baroreceptor signal or a change in the baroreceptor signalto thereby effect a change in the baroreflex system. The baroreceptoractivation device may be activated, deactivated, or otherwise modulatedcontinuously, periodically, or episodically. The baroreceptor activationdevice may comprise a wide variety of devices which utilize mechanical,electrical, thermal, chemical, biological, or other means to activatethe baroreceptor. The baroreceptor may be activated directly, oractivated indirectly via the adjacent vascular tissue. The baroreceptoractivation device may be positioned inside the vascular lumen (i.e.,intravascularly), outside the vascular wall (i.e., extravascularly) orwithin the vascular wall (i.e., intramurally). The particular activationpatterns may be selected to mimic those which naturally occur in thevenous and cardiopulmonary vasculature, which conditions might vary fromthose characteristic of the arterial vasculature. In other cases, theactivation patterns may be different from the natural patterns andselected to achieve an optimized barosystem response.

A control system may be used to generate a control signal whichactivates, deactivates or otherwise modulates the baroreceptoractivation device. The control system may operate in an open-loop or aclosed-loop mode. For example, in the open-loop mode, the patient and/orphysician may directly or remotely interface with the control system toprescribe the control signal. In the closed-loop mode, the controlsignal may be responsive to feedback from a sensor, wherein the responseis dictated by a preset or programmable algorithm.

To address low blood pressure and other conditions requiring bloodpressure augmentation, the present invention provides a number ofdevices, systems and methods by which the blood pressure may beselectively and controllably regulated by inhibiting or dampeningbaroreceptor signals. By selectively and controllably inhibiting ordampening baroreceptor signals, the present invention reduces conditionsassociated with low blood pressure.

To address hypertension, heart failure, cardiac arrhythmias, and theirassociated cardiovascular and nervous system disorders, the presentinvention provides a number of devices, systems and methods by which theblood pressure, nervous system activity, and neurohormonal activity maybe selectively and controllably regulated by activating baroreceptors,baroreceptor-like mechanoreceptors or pressoreceptors, or the like. Byselectively and controllably activating baroreceptors, the presentinvention reduces excessive blood pressure, sympathetic nervous systemactivation and neurohormonal activation, thereby minimizing theirdeleterious effects on the heart, vasculature and other organs andtissues.

In an exemplary embodiment, the present invention provides a system andmethod for treating a patient by inducing a baroreceptor signal toeffect a change in the baroreflex system (e.g., reduced heart rate,reduced blood pressure, etc.). The baroreceptor signal is activated orotherwise modified by selectively activating baroreceptors. Toaccomplish this, the system and method of the present invention utilizea baroreceptor activation device positioned near a baroreceptor in avein, the pulmonary vasculature, in a heart chamber, at a veno-atrialjunction, or the like.

Generally speaking, the baroreceptor activation device may be activated,deactivated or otherwise modulated to activate one or more baroreceptorsand induce a baroreceptor signal or a change in the baroreceptor signalto thereby effect a change in the baroreflex system. The baroreceptoractivation device may be activated, deactivated, or otherwise modulatedcontinuously, periodically, or episodically. The baroreceptor activationdevice may comprise a wide variety of devices which utilize mechanical,electrical, thermal, chemical, biological, or other means to activatethe baroreceptor. The baroreceptor may be activated directly, oractivated indirectly via the adjacent vascular tissue. The baroreceptoractivation device may be positioned inside the vascular lumen (i.e.,intravascularly), outside the vascular wall (i.e., extravascularly) orwithin the vascular wall (i.e., intramurally).

A control system may be used to generate a control signal whichactivates, deactivates or otherwise modulates the baroreceptoractivation device. The control system may operate in an open-loop or aclosed-loop mode. For example, in the open-loop mode, the patient and/orphysician may directly or remotely interface with the control system toprescribe the control signal. In the closed-loop mode, the controlsignal may be responsive to feedback from a sensor, wherein the responseis dictated by a preset or programmable algorithm.

To address low blood pressure and other conditions requiring bloodpressure augmentation, the present invention provides a number ofdevices, systems and methods by which the blood pressure may beselectively and controllably regulated by inhibiting or dampeningbaroreceptor signals. By selectively and controllably inhibiting ordampening baroreceptor signals, the present invention reduces conditionsassociated with low blood pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the upper torso of a human bodyshowing the major arteries and veins and associated anatomy.

FIG. 1A is a schematic illustration of the lower abdominal vasculatureincluding the abdominal aorta and the inferior vena cava.

FIG. 2 is a cross-sectional schematic illustration of baroreceptorswithin a vascular wall.

FIG. 3 is a schematic illustration of a baroreceptor activation systemin accordance with the present invention.

FIG. 4 is a schematic illustration of a baroreceptor activation devicein the form of an internal inflatable balloon which mechanically inducesa baroreceptor signal in accordance with an embodiment of the presentinvention.

FIG. 5 is a schematic illustration of a baroreceptor activation devicein the form of an external pressure cuff which mechanically induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIG. 6 is a schematic illustration of a baroreceptor activation devicein the form of an internal deformable coil structure which mechanicallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention.

FIGS. 6B and 6C are cross-sectional views of alternative embodiments ofthe coil member illustrated in FIG. 6.

FIG. 7 is a schematic illustration of a baroreceptor activation devicein the form of an external deformable coil structure which mechanicallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention.

FIG. 8 is a schematic illustration of a baroreceptor activation devicein the form of an external flow regulator which artificially createsback pressure to induce a baroreceptor signal in accordance with anembodiment of the present invention.

FIG. 9 is a schematic illustration of a baroreceptor activation devicein the form of an internal flow regulator which artificially createsback pressure to induce a baroreceptor signal in accordance with anembodiment of the present invention.

FIG. 10 is a schematic illustration of a baroreceptor activation devicein the form of a magnetic device which mechanically induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIG. 11 is a schematic illustration of a baroreceptor activation devicein the form of a transducer which mechanically induces a baroreceptorsignal in accordance with an embodiment of the present invention.

FIG. 12 is a schematic illustration of a baroreceptor activation devicein the form of a fluid delivery device which may be used to deliver anagent which chemically or biologically induces a baroreceptor signal inaccordance with an embodiment of the present invention.

FIG. 13 is a schematic illustration of a baroreceptor activation devicein the form of an internal conductive structure which electrically orthermally induces a baroreceptor signal in accordance with an embodimentof the present invention.

FIG. 14 is a schematic illustration of a baroreceptor activation devicein the form of an internal conductive structure, activated by aninternal inductor, which electrically or thermally induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIG. 15 is a schematic illustration of a baroreceptor activation devicein the form of an internal conductive structure, activated by aninternal inductor located in an adjacent vessel, which electrically orthermally induces a baroreceptor signal in accordance with an embodimentof the present invention.

FIG. 16 is a schematic illustration of a baroreceptor activation devicein the form of an internal conductive structure, activated by anexternal inductor, which electrically or thermally induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIG. 17 is a schematic illustration of a baroreceptor activation devicein the form of an external conductive structure which electrically orthermally induces a baroreceptor signal in accordance with an embodimentof the present invention.

FIG. 18 is a schematic illustration of a baroreceptor activation devicein the form of an internal bipolar conductive structure whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention.

FIG. 19 is a schematic illustration of a baroreceptor activation devicein the form of an electromagnetic field responsive device whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention.

FIG. 20 is a schematic illustration of a baroreceptor activation devicein the form of an external Peltier device which thermally induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIGS. 21A-21C are schematic illustrations of a preferred embodiment ofan inductively activated electrically conductive structure.

FIGS. 22A-22C are ECG charts of a dog undergoing stimulation of theabdominal IVC.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

To better understand the present invention, it may be useful to explainsome of the basic vascular anatomy associated with the cardiovascularsystem. Refer to FIG. 1 which is a schematic illustration of the uppertorso of a human body 10 showing some of the major arteries and veins ofthe cardiovascular system. The left ventricle of the heart 11 pumpsoxygenated blood up into the aortic arch 12. The right subclavian artery13, the right common carotid artery 14, the left common carotid artery15 and the left subclavian artery 16 branch off the aortic arch 12proximal of the descending thoracic aorta 17. Although relatively short,a distinct vascular segment referred to as the brachiocephalic artery 22connects the right subclavian artery 13 and the right common carotidartery 14 to the aortic arch 12. The right carotid artery 14 bifurcatesinto the right external carotid artery 18 and the right internal carotidartery 19 at the right carotid sinus 20. Although not shown for purposesof clarity only, the left carotid artery 15 similarly bifurcates intothe left external carotid artery and the left internal carotid artery atthe left carotid sinus.

From the aortic arch 12, oxygenated blood flows into the carotidarteries 18/19 and the subclavian arteries 13/16. From the carotidarteries 18/19, oxygenated blood circulates through the head andcerebral vasculature and oxygen depleted blood returns to the heart 11by way of the jugular veins, of which only the right internal jugularvein 21 is shown for sake of clarity. From the subclavian arteries13/16, oxygenated blood circulates through the upper peripheralvasculature and oxygen depleted blood returns to the heart by way of thesubclavian veins, of which only the right subclavian vein 23 is shown,also for sake of clarity. Deoxygenated blood from the upper torso andhead eventually return to the heart 11 through the superior vena cava23.1, shown diagrammatically only. The heart 11 pumps theoxygen-depleted blood through the pulmonary system where it isre-oxygenated. The re-oxygenated blood returns to the heart 11 whichpumps the re-oxygenated blood into the aortic arch as described above,and the cycle repeats. In the abdomen and lower extremities, oxygenatedblood is delivered to the organs and lower limbs through the abdominalaorta 23.2. Deoxygenated blood returns to the heart through the inferiorvena cava 23.3.

Within the walls of many veins, the pulmonary vasculature and thechambers of the heart, as in the walls of the carotid sinus, aorta andother arterial structures, there are baroreceptors. Baroreceptors are atype of stretch receptor used by the body to sense blood pressure andblood volume. An increase in blood pressure or volume causes thevascular wall to stretch, and a decrease in blood pressure or volumecauses the vascular wall to return to its original size. In manyvessels, such a cycle is repeated with each beat of the heart. Inothers, in particular some of the body's veins, the pressure and volumechange more slowly. Because baroreceptors are located within thevascular wall, they are able to sense deformation of the adjacenttissue, which is indicative of a change in blood pressure or volume.

Refer now to FIG. 2, which shows a schematic illustration ofbaroreceptors 30 disposed in a generic vascular wall 40 and a schematicflow chart of the baroreflex system 50. Baroreceptors 30 are profuselydistributed within the arterial walls 40 of the blood vessels majorarteries discussed previously, and are presently believed by theinventors to form an arbor 32 as is characteristic of the analogousreceptors in the arterial system as described in parent application Ser.No. 09/672,850, previously incorporated herein by reference. Abaroreceptor arbor 32 would comprise a plurality of baroreceptors 30,each of which transmits baroreceptor signals to the brain 52 via nerve38. The baroreceptors 30 may be so profusely distributed and arborizedwithin the vascular wall 40 that discrete baroreceptor arbors 32 are notreadily discernable. To this end, those skilled in the art willappreciate that the baroreceptors 30 shown in FIG. 2 are primarilyschematic for purposes of illustration and discussion. In other regions,the baroreceptors may be so sparsely distributed that activation over arelatively greater length of the vein would be required than would bewith an artery where the receptors might be more concentrated.

Baroreceptor signals in the arterial vasculature are used to activate anumber of body systems which collectively may be referred to as thebaroreflex system 50. For the purposes of the present invention, it willbe assumed that the “receptors” in the venous and cardiopulmonaryvasculature and heart chambers function analogously to the baroreceptorsin the arterial vasculature, but such assumption is not intended tolimit the present invention in any way. In particular, the methodsdescribed herein will function and achieve at least some of the statedtherapeutic objectives regardless of the precise and actual mechanismresponsible for the result. Moreover, the present invention may activatebaroreceptors, mechanoreceptors, pressoreceptors, or any other venousheart, or cardiopulmonary receptors which affect the blood pressure,nervous system activity, and neurohormonal activity in a manneranalogous to baroreceptors in the arterial vasculation. For convenience,all such venous receptors will be referred to collectively herein as“baroreceptors.” Thus for discussion purposes, it will be assumed thatbaroreceptors 30 are connected to the brain 52 via the nervous system51. Thus, the brain 52 is able to detect changes in blood pressure whichare indicative of cardiac output and/or blood volume. If cardiac outputand/or blood volume are insufficient to meet demand (i.e., the heart 11is unable to pump sufficient blood), the baroreflex system 50 activatesa number of body systems, including the heart 11, kidneys 53, vessels54, and other organs/tissues. Such activation of the baroreflex system50 generally corresponds to an increase in neurohormonal activity.Specifically, the baroreflex system 50 initiates a neurohormonalsequence that signals the heart 11 to increase heart rate and increasecontraction force in order to increase cardiac output, signals thekidneys 53 to increase blood volume by retaining sodium and water, andsignals the vessels 54 to constrict to elevate blood pressure. Thecardiac, renal and vascular responses increase blood pressure andcardiac output 55, and thus increase the workload of the heart 11. In apatient with heart failure, this further accelerates myocardial damageand exacerbates the heart failure state.

To address the problems of hypertension, heart failure, cardiacarrhythmias, renal dysfunction, and nervous system other cardiovasculardisorders, the present invention basically provides a number of devices,systems and methods by which the baroreflex system 50 is activated toreduce excessive blood pressure, autonomic nervous system activity andneurohormonal activation. In particular, the present invention providesa number of devices, systems and methods by which baroreceptors 30 maybe activated, thereby indicating an increase in blood pressure andsignaling the brain 52 to reduce the body's blood pressure and level ofsympathetic nervous system and neurohormonal activation, and increaseparasypathetic nervous system activation, thus having a beneficialeffect on the cardiovascular system and other body systems.

With reference to FIG. 3, the present invention generally provides asystem including a control system 60, a baroreceptor activation device70, and a sensor 80 (optional). For purposes of illustration, thebaroreceptor activation device 70 is shown to be located on, in or nearthe inferior vena cava 23.3, but it could also be located at the otherbaroreceptor target locations discussed elsewhere in this application.The exemplary control system 60, generally operates in the followingmanner. The sensor 80 senses and/or monitors a parameter (e.g.,cardiovascular function) indicative of the need to modify the baroreflexsystem and generates a signal indicative of the parameter. The controlsystem 60 generates a control signal as a function of the receivedsensor signal. The control signal activates, deactivates or otherwisemodulates the baroreceptor activation device 70. Typically, activationof the device 70 results in activation of the baroreceptors 30 (FIG. 2).Alternatively, deactivation or modulation of the baroreceptor activationdevice 70 may cause or modify activation of the baroreceptors 30. Thebaroreceptor activation device 70 may comprise a wide variety of deviceswhich utilize mechanical, electrical, thermal, chemical, biological, orother means to activate baroreceptors 30. Thus, when the sensor 80detects a parameter indicative of the need to modify the baroreflexsystem activity (e.g., excessive blood pressure), the control system 60generates a control signal to modulate (e.g. activate) the baroreceptoractivation device 70 thereby inducing a baroreceptor 30 signal that isperceived by the brain 52 to be apparent excessive blood pressure. Whenthe sensor 80 detects a parameter indicative of normal body function(e.g., normal blood pressure), the control system 60 generates a controlsignal to modulate (e.g., deactivate) the baroreceptor activation device70.

As mentioned previously, the baroreceptor activation device 70 maycomprise a wide variety of devices which utilize mechanical, electrical,thermal, chemical, biological or other means to activate thebaroreceptors 30. Specific embodiments of the generic baroreceptoractivation device 70 are discussed with reference to FIGS. 4-21. In mostinstances, particularly the mechanical activation embodiments, thebaroreceptor activation device 70 indirectly activates one or morebaroreceptors 30 by stretching or otherwise deforming the vascular wall40 surrounding the baroreceptors 30. In some other instances,particularly the non-mechanical activation embodiments, the baroreceptoractivation device 70 may directly activate one or more baroreceptors 30by changing the electrical, thermal or chemical environment or potentialacross the baroreceptors 30. It is also possible that changing theelectrical, thermal or chemical potential across the tissue surroundingthe baroreceptors 30 may cause the surrounding tissue to stretch orotherwise deform, thus mechanically activating the baroreceptors 30. Inother instances, particularly the biological activation embodiments, achange in the function or sensitivity of the baroreceptors 30 may beinduced by changing the biological activity in the baroreceptors 30 andaltering their intracellular makeup and function.

All of the specific embodiments of the baroreceptor activation device 70are suitable for implantation, and are preferably implanted using aminimally invasive percutaneous transluminal approach and/or a minimallyinvasive surgical approach, depending on whether the device 70 isdisposed intravascularly, extravascularly or within the vascular wall40. The baroreceptor activation device 70 may be positioned anywhere inor proximate the venous or cardiopulmonary vasculature, and/or the heartchambers, where baroreceptors capable of modulating the baroreflexsystem 50 are present. The baroreceptor activation device 70 willusually be implanted such that the device 70 is positioned immediatelyadjacent the baroreceptors 30. Alternatively, the baroreceptoractivation device 70 may be outside the body such that the device 70 ispositioned a short distance from but proximate to the baroreceptors 30.Preferably, the baroreceptor activation device 70 is implanted at alocation which permits selective activation of the target baroreceptor,typically being in, around, or near the target baroreceptor. Forpurposes of illustration only, the present invention is described withreference to baroreceptor activation device 70 positioned near theinferior vena cava 23.3.

The optional sensor 80 is operably coupled to the control system 60 byelectric sensor cable or lead 82. The sensor 80 may comprise anysuitable device that measures or monitors a parameter indicative of theneed to modify the activity of the baroreflex system. For example, thesensor 80 may comprise a physiologic transducer or gauge that measuresECG, blood pressure (systolic, diastolic, average or pulse pressure),blood volumetric flow rate, blood flow velocity, blood pH, O2 or CO2content, mixed venous oxygen saturation (SVO2), vasoactivity, nerveactivity, tissue activity or composition. Examples of suitabletransducers or gauges for the sensor 80 include ECG electrodes, apiezoelectric pressure transducer, an ultrasonic flow velocitytransducer, an ultrasonic volumetric flow rate transducer, athermodilution flow velocity transducer, a capacitive pressuretransducer, a membrane pH electrode, an optical detector (SVO2) or astrain gage. Although only one sensor 80 is shown, multiple sensors 80of the same or different type at the same or different locations may beutilized.

The sensor 80 is preferably positioned in a chamber of the heart 11, orin/on a major artery such as the aortic arch 12, a common carotid artery14/15, a subclavian artery 13/16 or the brachiocephalic artery 22, or inany of the low-pressure venous or cardiopulmonary sites, such that theparameter of interest may be readily ascertained. The sensor 80 may bedisposed inside the body such as in or on an artery, a vein or a nerve(e.g. vagus nerve), or disposed outside the body, depending on the typeof transducer or gauge utilized. The sensor 80 may be separate from thebaroreceptor activation device 70 or combined therewith. For purposes ofillustration only, the sensor 80 is shown positioned on the rightsubclavian artery 13.

By way of example, the control system 60 includes a control block 61comprising a processor 63 and a memory 62. Control system 60 isconnected to the sensor 80 by way of sensor cable 82. Control system 60is also connected to the baroreceptor activation device 70 by way ofelectric control cable 72. Thus, the control system 60 receives a sensorsignal from the sensor 80 by way of sensor cable 82, and transmits acontrol signal to the baroreceptor activation device 70 by way ofcontrol cable 72.

The memory 62 may contain data related to the sensor signal, the controlsignal, and/or values and commands provided by the input device 64. Thememory 62 may also include software containing one or more algorithmsdefining one or more functions or relationships between the controlsignal and the sensor signal. The algorithm may dictate activation ordeactivation control signals depending on the sensor signal or amathematical derivative thereof. The algorithm may dictate an activationor deactivation control signal when the sensor signal falls below alower predetermined threshold value, rises above an upper predeterminedthreshold value or when the sensor signal indicates a specificphysiologic event.

As mentioned previously, the baroreceptor activation device 70 mayactivate baroreceptors 30 mechanically, electrically, thermally,chemically, biologically or otherwise. In some instances, the controlsystem 60 includes a driver 66 to provide the desired power mode for thebaroreceptor activation device 70. For example if the baroreceptoractivation device 70 utilizes pneumatic or hydraulic actuation, thedriver 66 may comprise a pressure/vacuum source and the cable 72 maycomprise fluid line(s). If the baroreceptor activation device 70utilizes electrical or thermal actuation, the driver 66 may comprise apower amplifier or the like and the cable 72 may comprise electricallead(s). If the baroreceptor activation device 70 utilizes chemical orbiological actuation, the driver 66 may comprise a fluid reservoir and apressure/vacuum source, and the cable 72 may comprise fluid line(s). Inother instances, the driver 66 may not be necessary, particularly if theprocessor 63 generates a sufficiently strong electrical signal for lowlevel electrical or thermal actuation of the baroreceptor activationdevice 70.

The control system 60 may operate as a closed loop utilizing feedbackfrom the sensor 80, or as an open loop utilizing commands received byinput device 64. The open loop operation of the control system 60preferably utilizes some feedback from the transducer 80, but may alsooperate without feedback. Commands received by the input device 64 maydirectly influence the control signal or may alter the software andrelated algorithms contained in memory 62. The patient and/or treatingphysician may provide commands to input device 64. Display 65 may beused to view the sensor signal, control signal and/or the software/datacontained in memory 62.

The control signal generated by the control system 60 may be continuous,periodic, episodic or a combination thereof, as dictated by an algorithmcontained in memory 62. Continuous control signals include a constantpulse, a constant train of pulses, a triggered pulse and a triggeredtrain of pulses. Examples of periodic control signals include each ofthe continuous control signals described above which have a designatedstart time (e.g., beginning of each minute, hour or day) and adesignated duration (e.g., 1 second, 1 minute, 1 hour). Examples ofepisodic control signals include each of the continuous control signalsdescribed above which are triggered by an episode (e.g., activation bythe patient/physician, an increase in blood pressure above a certainthreshold, etc.).

The control system 60 may be implanted in whole or in part. For example,the entire control system 60 may be carried externally by the patientutilizing transdermal connections to the sensor lead 82 and the controllead 72. Alternatively, the control block 61 and driver 66 may beimplanted with the input device 64 and display 65 carried externally bythe patient utilizing transdermal connections therebetween. As a furtheralternative, the transdermal connections may be replaced by cooperatingtransmitters/receivers to remotely communicate between components of thecontrol system 60 and/or the sensor 80 and baroreceptor activationdevice 70.

With general reference to FIGS. 4-21, schematic illustrations ofspecific embodiments of the baroreceptor activation device 70 are shown.The design, function and use of these specific embodiments, in additionto the control system 60 and sensor 80 (not shown), are the same asdescribed with reference to FIG. 3, unless otherwise noted or apparentfrom the description. In addition, the anatomical features illustratedin FIGS. 4-20 are the same as discussed with reference to FIGS. 1, 1A,and 2, unless otherwise noted. In each embodiment, the connectionsbetween the components 60/70/80 may be physical (e.g., wires, tubes,cables, etc.) or remote (e.g., transmitter/receiver, inductive,magnetic, etc.). For physical connections, the connection may travelintraarterially, intravenously, subcutaneously, or through other naturaltissue paths.

Refer now to FIG. 4 which shows schematic illustrations of abaroreceptor activation device 100 in the form of an intravascularinflatable balloon 100. The inflatable balloon device 100 includes ahelical balloon 102 which is connected to a fluid line 104. An exampleof a similar helical balloon is disclosed in U.S. Pat. No. 5,181,911 toShturman, the entire disclosure of which is hereby incorporated byreference. The balloon 102 preferably has a helical geometry or anyother geometry which allows blood perfusion therethrough. The fluid line104 is connected to the driver 66 of the control system 60 (FIG. 3). Inthis embodiment, the driver 66 comprises a pressure/vacuum source (i.e.,an inflation device) which selectively inflates and deflates the helicalballoon 102. Upon inflation, the helical balloon 102 expands, preferablyincreasing in outside diameter only, to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon deflation, the helical balloon 102 returns to itsrelaxed geometry such that the vascular wall 40 returns to its nominalstate. Thus, by selectively inflating the helical balloon 102, thebaroreceptors 30 adjacent thereto may be selectively activated.

As an alternative to pneumatic or hydraulic expansion utilizing aballoon, a mechanical expansion device (not shown) may be used to expandor dilate the vascular wall 40 and thereby mechanically activate thebaroreceptors 30. For example, the mechanical expansion device maycomprise a tubular wire braid structure that diametrically expands whenlongitudinally compressed as disclosed in U.S. Pat. No. 5,222,971 toWillard et al., the entire disclosure of which is hereby incorporated byreference. The tubular braid may be disposed intravascularly and permitsblood perfusion through the wire mesh. In this embodiment, the driver 66may comprise a linear actuator connected by actuation cables to oppositeends of the braid. When the opposite ends of the tubular braid arebrought closer together by actuation of the cables, the diameter of thebraid increases to expand the vascular wall 40 and activate thebaroreceptors 30.

Refer now to FIG. 5 which shows a baroreceptor activation device 120 inthe form of an extravascular pressure cuff 120. The pressure cuff device120 includes an inflatable cuff 122 which is connected to a fluid line124. Examples of a similar cuffs 122 are disclosed in U.S. Pat. No.4,256,094 to Kapp et al. and U.S. Pat. No. 4,881,939 to Newman, theentire disclosures of which are hereby incorporated by reference. Thefluid line 124 is connected to the driver 66 (FIG. 3) of the controlsystem 60. In this embodiment, the driver 66 comprises a pressure/vacuumsource (i.e., an inflation device) which selectively inflates anddeflates the cuff 122. Upon inflation, the cuff 122 expands, preferablyincreasing in inside diameter only, to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon deflation, the cuff 122 returns to its relaxedgeometry such that the vascular wall 40 returns to its nominal state.Thus, by selectively inflating the inflatable cuff 122, thebaroreceptors 30 adjacent thereto may be selectively activated.

The driver 66 may be automatically actuated by the control system 60 asdiscussed above, or may be manually actuated. An example of anexternally manually actuated pressure/vacuum source is disclosed in U.S.Pat. No. 4,709,690 to Haber, the entire disclosure of which is herebyincorporated by reference. Examples of transdermally manually actuatedpressure/vacuum sources are disclosed in U.S. Pat. No. 4,586,501 toClaracq, U.S. Pat. No. 4,828,544 to Lane et al., and U.S. Pat. No.5,634,878 to Grundei et al., the entire disclosures of which are herebyincorporated by reference.

Those skilled in the art will recognize that other external compressiondevices may be used in place of the inflatable cuff device 120. Forexample, a piston actuated by a solenoid may apply compression to thevascular wall. An example of a solenoid actuated piston device isdisclosed in U.S. Pat. No. 4,014,318 to Dokum et al, and an example of ahydraulically or pneumatically actuated piston device is disclosed inU.S. Pat. No. 4,586,501 to Claracq, the entire disclosures of which arehereby incorporated by reference. Other examples include a rotary ringcompression device as disclosed in U.S. Pat. No. 4,551,862 to Haber, andan electromagnetically actuated compression ring device as disclosed inU.S. Pat. No. 5,509,888 to Miller, the entire disclosures of which arehereby incorporated by reference.

Refer now to FIG. 6 which shows a baroreceptor activation device 140 inthe form of an intravascular deformable structure. The deformablestructure device 140 includes a coil, braid or other stent-likestructure 142 disposed in the vascular lumen. The deformable structure142 includes one or more individual structural members connected to anelectrical lead 144. Each of the structural members forming deformablestructure 142 may comprise a shape memory material 146 (e.g., nickeltitanium alloy) as illustrated in FIG. 6B, or a bimetallic material 148as illustrated in FIG. 6C. The electrical lead 144 is connected to thedriver 66 of the control system 60. In this embodiment, the driver 66comprises an electric power generator or amplifier which selectivelydelivers electric current to the structure 142 which resistively heatsthe structural members 146/148. The structure 142 may be unipolar asshown using the surrounding tissue as ground, or bipolar or multipolarusing leads connected to either end of the structure 142. Electricalpower may also be delivered to the structure 142 inductively asdescribed hereinafter with reference to FIGS. 14-16.

Upon application of electrical current to the shape memory material 146,it is resistively heated causing a phase change and a correspondingchange in shape. Upon application of electrical current to thebimetallic material 148, it is resistively heated causing a differentialin thermal expansion and a corresponding change in shape. In eithercase, the material 146/148 is designed such that the change in shapecauses expansion of the structure 142 to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon removal of the electrical current, the material146/148 cools and the structure 142 returns to its relaxed geometry suchthat the baroreceptors 30 and/or the vascular wall 40 return to theirnominal state. Thus, by selectively expanding the structure 142, thebaroreceptors 30 adjacent thereto may be selectively activated.

Refer now to FIG. 7 which shows a baroreceptor activation device 160 inthe form of an extravascular deformable structure. The extravasculardeformable structure device 160 is substantially the same as theintravascular deformable structure device 140 described with referenceto FIGS. 6A and 6B, except that the extravascular device 160 is disposedabout the vascular wall, and therefore compresses, rather than expands,the vascular wall 40. The deformable structure device 160 includes acoil, braid or other stent-like structure 162 comprising one or moreindividual structural members connected to an electrical lead 164. Eachof the structural members may comprise a shape memory material 166(e.g., nickel titanium alloy) as illustrated in FIG. 7C, or a bimetallicmaterial 168. The structure 162 may be unipolar as shown using thesurrounding tissue as ground, or bipolar or multipolar using leadsconnected to either end of the structure 162. Electrical power may alsobe delivered to the structure 162 inductively as described hereinafterwith reference to FIGS. 14-16.

Upon application of electrical current to the shape memory material 166,it is resistively heated causing a phase change and a correspondingchange in shape. Upon application of electrical current to thebimetallic material 168, it is resistively heated causing a differentialin thermal expansion and a corresponding change in shape. In eithercase, the material 166/168 is designed such that the change in shapecauses constriction of the structure 162 to mechanically activatebaroreceptors 30 by compressing or otherwise deforming the baroreceptors30 and/or the vascular wall 40. Upon removal of the electrical current,the material 166/168 cools and the structure 162 returns to its relaxedgeometry such that the baroreceptors 30 and/or the vascular wall 40return to their nominal state. Thus, by selectively compressing thestructure 162, the baroreceptors 30 adjacent thereto may be selectivelyactivated.

Refer now to FIG. 8 which shows a baroreceptor activation device 180 inthe form of an extravascular flow regulator which artificially createsback pressure adjacent the baroreceptors 30. The flow regulator device180 includes an external compression device 182, which may comprise anyof the external compression devices described with reference to FIG. 5.The external compression device 182 is operably connected to the driver66 of the control system 60 by way of cable 184, which may comprise afluid line or electrical lead, depending on the type of externalcompression device 182 utilized. The external compression device 182 isdisposed about the vascular wall distal of the baroreceptors 30. Forexample, the external compression device 182 may be located in thedistal portions of the inferior vena cava 23.3 to create back pressureadjacent the baroreceptors 30 upstream in the inferior vena cava.

Upon actuation of the external compression device 182, the vascular wallis constricted thereby reducing the size of the vascular lumen therein.By reducing the size of the vascular lumen, pressure proximal of theexternal compression device 182 is increased thereby expanding thevascular wall. Thus, by selectively activating the external compressiondevice 182 to constrict the vascular lumen and create back pressure, thebaroreceptors 30 may be selectively activated.

Refer now to FIG. 9 which shows a baroreceptor activation device 200 inthe form of an intravascular flow regular which artificially createsback pressure adjacent the baroreceptors 30. The intravascular flowregulator device 200 is substantially similar in function and use asextravascular flow regulator 180 described with reference to FIG. 8,except that the intravascular flow regulator device 200 is disposed inthe vascular lumen.

Intravascular flow regulator 200 includes an internal valve 202 to atleast partially close the vascular lumen distal of the baroreceptors 30.By at least partially closing the vascular lumen distal of thebaroreceptors 30, back pressure is created proximal of the internalvalve 202 such that the vascular wall expands to activate thebaroreceptors 30. The internal valve 202 may be positioned at any of thelocations described with reference to the external compression device182, except that the internal valve 202 is placed within the vascularlumen. Specifically, the internal compression device 202 may be locatedin the distal portions of the vasculature to create back pressureadjacent to the baroreceptors 30 in the veins or cardiopulmonary system.

The internal valve 202 is operably coupled to the driver 66 of thecontrol system 60 by way of electrical lead 204. The control system 60may selectively open, close or change the flow resistance of the valve202 as described in more detail hereinafter. The internal valve 202 mayinclude valve leaflets 206 (bi-leaflet or tri-leaflet) which rotateinside housing 208 about an axis between an open position and a closedposition. The closed position may be completely closed or partiallyclosed, depending on the desired amount of back pressure to be created.The opening and closing of the internal valve 202 may be selectivelycontrolled by altering the resistance of leaflet 206 rotation or byaltering the opening force of the leaflets 206. The resistance ofrotation of the leaflets 206 may be altered utilizingelectromagnetically actuated metallic bearings carried by the housing208. The opening force of the leaflets 206 may be altered by utilizingelectromagnetic coils in each of the leaflets to selectively magnetizethe leaflets such that they either repel or attract each other, therebyfacilitating valve opening and closing, respectively.

A wide variety of intravascular flow regulators may be used in place ofinternal valve 202. For example, internal inflatable balloon devices asdisclosed in U.S. Pat. No. 4,682,583 to Burton et al. and U.S. Pat. No.5,634,878 to Grundei et al., the entire disclosures of which is herebyincorporated by reference, may be adapted for use in place of valve 202.Such inflatable balloon devices may be operated in a similar manner asthe inflatable cuff 122 described with reference to FIG. 5.Specifically, in this embodiment, the driver 66 would comprises apressure/vacuum source (i.e., an inflation device) which selectivelyinflates and deflates the internal balloon. Upon inflation, the balloonexpands to partially occlude blood flow and create back pressure tomechanically activate baroreceptors 30 by stretching or otherwisedeforming them and/or the vascular wall 40. Upon deflation, the internalballoon returns to its normal profile such that flow is not hindered andback pressure is eliminated. Thus, by selectively inflating the internalballoon, the baroreceptors 30 proximal thereof may be selectivelyactivated by creating back pressure.

Refer now to FIG. 10 which shows a baroreceptor activation device 220 inthe form of magnetic particles 222 disposed in the vascular wall 40. Themagnetic particles 222 may comprise magnetically responsive materials(i.e., ferrous based materials) and may be magnetically neutral ormagnetically active. Preferably, the magnetic particles 222 comprisepermanent magnets having an elongate cylinder shape with north and southpoles to strongly respond to magnetic fields. The magnetic particles 222are actuated by an electromagnetic coil 224 which is operably coupled tothe driver 66 of the control system 60 by way of an electrical cable226. The electromagnetic coil 224 may be implanted as shown, or locatedoutside the body, in which case the driver 66 and the remainder of thecontrol system 60 would also be located outside the body. By selectivelyactivating the electromagnetic coil 224 to create a magnetic field, themagnetic particles 222 may be repelled, attracted or rotated.Alternatively, the magnetic field created by the electromagnetic coil224 may be alternated such that the magnetic particles 222 vibratewithin the vascular wall 40. When the magnetic particles are repelled,attracted, rotated, vibrated or otherwise moved by the magnetic fieldcreated by the electromagnetic coil 224, the baroreceptors 30 aremechanically activated.

The electromagnetic coil 224 is preferably placed as close as possibleto the magnetic particles 222 in the vascular wall 40, and may be placedintravascularly, extravascularly, or in any of the alternative locationsdiscussed with reference to inductor shown in FIGS. 14-16. The magneticparticles 222 may be implanted in the vascular wall 40 by injecting aferro-fluid or a ferro-particle suspension into the vascular walladjacent to the baroreceptors 30. To increase biocompatibility, theparticles 222 may be coated with a ceramic, polymeric or other inertmaterial. Injection of the fluid carrying the magnetic particles 222 ispreferably performed percutaneously.

Refer now to FIG. 11 which shows a baroreceptor activation device 240 inthe form of one or more transducers 242. Preferably, the transducers 242comprise an array surrounding the vascular wall. The transducers 242 maybe intravascularly or extravascularly positioned adjacent to thebaroreceptors 30. In this embodiment, the transducers 242 comprisedevices which convert electrical signals into some physical phenomena,such as mechanical vibration or acoustic waves. The electrical signalsare provided to the transducers 242 by way of electrical cables 244which are connected to the driver 66 of the control system 60. Byselectively activating the transducers 242 to create a physicalphenomena, the baroreceptors 30 may be mechanically activated.

The transducers 242 may comprise an acoustic transmitter which transmitssonic or ultrasonic sound waves into the vascular wall 40 to activatethe baroreceptors 30. Alternatively, the transducers 242 may comprise apiezoelectric material which vibrates the vascular wall to activate thebaroreceptors 30. As a further alternative, the transducers 242 maycomprise an artificial muscle which deflects upon application of anelectrical signal. An example of an artificial muscle transducercomprises plastic impregnated with a lithium-perchlorate electrolytedisposed between sheets of polypyrrole, a conductive polymer. Suchplastic muscles may be electrically activated to cause deflection indifferent directions depending on the polarity of the applied current.

Refer now to FIG. 12 which shows a baroreceptor activation device 260 inthe form of a local fluid delivery device 262 suitable for delivering achemical or biological fluid agent to the vascular wall adjacent thebaroreceptors 30. The local fluid delivery device 262 may be locatedintravascularly, extravascularly, or intramurally. For purposes ofillustration only, the local fluid delivery device 262 is positionedextravascularly.

The local fluid delivery device 262 may include proximal and distalseals 266 which retain the fluid agent disposed in the lumen or cavity268 adjacent to vascular wall. Preferably, the local fluid deliverydevice 262 completely surrounds the vascular wall 40 to maintain aneffective seal. Those skilled in the art will recognize that the localfluid delivery device 262 may comprise a wide variety of implantabledrug delivery devices or pumps known in the art.

The local fluid delivery device 260 is connected to a fluid line 264which is connected to the driver 66 of the control system 60. In thisembodiment, the driver 66 comprises a pressure/vacuum source and fluidreservoir containing the desired chemical or biological fluid agent. Thechemical or biological fluid agent may comprise a wide variety ofstimulatory substances. Examples include veratridine, bradykinin,prostaglandins, and related substances. Such stimulatory substancesactivate the baroreceptors 30 directly or enhance their sensitivity toother stimuli and therefore may be used in combination with the otherbaroreceptor activation devices described herein. Other examples includegrowth factors and other agents that modify the function of thebaroreceptors 30 or the cells of the vascular tissue surrounding thebaroreceptors 30 causing the baroreceptors 30 to be activated or causingalteration of their responsiveness or activation pattern to otherstimuli. It is also contemplated that injectable stimulators that areinduced remotely, as described in U.S. Pat. No. 6,061,596 which isincorporated herein by reference, may be used with the presentinvention.

As an alternative, the fluid delivery device 260 may be used to delivera photochemical that is essentially inert until activated by light tohave a stimulatory effect as described above. In this embodiment, thefluid delivery device 260 would include a light source such as a lightemitting diode (LED), and the driver 66 of the control system 60 wouldinclude a pulse generator for the LED combined with a pressure/vacuumsource and fluid reservoir described previously. The photochemical wouldbe delivered with the fluid delivery device 260 as described above, andthe photochemical would be activated, deactivated or modulated byactivating, deactivating or modulating the LED.

As a further alternative, the fluid delivery device 260 may be used todeliver a warm or hot fluid (e.g. saline) to thermally activate thebaroreceptors 30. In this embodiment, the driver 66 of the controlsystem 60 would include a heat generator for heating the fluid, combinedwith a pressure/vacuum source and fluid reservoir described previously.The hot or warm fluid would be delivered and preferably circulated withthe fluid delivery device 260 as described above, and the temperature ofthe fluid would be controlled by the driver 66.

Refer now to FIG. 13 which shows a baroreceptor activation device 280 inthe form of an intravascular electrically conductive structure orelectrode 282. The electrode structure 282 may comprise a self-expandingor balloon expandable coil, braid or other stent-like structure disposedin the vascular lumen. The electrode structure 282 may serve the dualpurpose of maintaining lumen patency while also delivering electricalstimuli. To this end, the electrode structure 282 may be implantedutilizing conventional intravascular stent and filter deliverytechniques. Preferably, the electrode structure 282 comprises a geometrywhich allows blood perfusion therethrough. The electrode structure 282comprises electrically conductive material which may be selectivelyinsulated to establish contact with the inside surface of the vascularwall 40 at desired locations, and limit extraneous electrical contactwith blood flowing through the vessel and other tissues.

The electrode structure 282 is connected to electric lead 284 which isconnected to the driver 66 of the control system 60. The driver 66, inthis embodiment, may comprise a power amplifier, pulse generator or thelike to selectively deliver electrical control signals to structure 282.As mentioned previously, the electrical control signal generated by thedriver 66 may be continuous, periodic, episodic or a combinationthereof, as dictated by an algorithm contained in memory 62 of thecontrol system 60. Continuous control signals include a constant pulse,a constant train of pulses, a triggered pulse and a triggered train ofpulses. Periodic control signals include each of the continuous controlsignals described above which have a designated start time and adesignated duration. Episodic control signals include each of thecontinuous control signals described above which are triggered by anepisode.

By selectively activating, deactivating or otherwise modulating theelectrical control signal transmitted to the electrode structure 282,electrical energy may be delivered to the vascular wall to activate thebaroreceptors 30. As discussed previously, activation of thebaroreceptors 30 may occur directly or indirectly. In particular, theelectrical signal delivered to the vascular wall 40 by the electrodestructure 282 may cause the vascular wall to stretch or otherwise deformthereby indirectly activating the baroreceptors 30 disposed therein.Alternatively, the electrical signals delivered to the vascular wall bythe electrode structure 282 may directly activate the baroreceptors 30by changing the electrical potential across the baroreceptors 30. Ineither case, the electrical signal is delivered to the vascular wall 40immediately adjacent to the baroreceptors 30. It is also contemplatedthat the electrode structure 282 may delivery thermal energy byutilizing a semi-conductive material having a higher resistance suchthat the electrode structure 282 resistively generates heat uponapplication of electrical energy.

Various alternative embodiments are contemplated for the electrodestructure 282, including its design, implanted location, and method ofelectrical activation. For example, the electrode structure 282 may beunipolar as shown in FIG. 13 using the surrounding tissue as ground, orbipolar using leads connected to either end of the structure 282 asshown in Figure. In the embodiment of FIGS. 18A and 18B, the electrodestructure 282 includes two or more individual electrically conductivemembers 283/285 which are electrically isolated at their respectivecross-over points utilizing insulative materials. Each of the members283/285 is connected to a separate conductor contained within theelectrical lead 284. Alternatively, an array of bipoles may be used asdescribed in more detail with reference to FIG. 21. As a furtheralternative, a multipolar arrangement may be used wherein three or moreelectrically conductive members are included in the structure 282. Forexample, a tripolar arrangement may be provided by one electricallyconductive member having a polarity disposed between two electricallyconductive members having the opposite polarity.

In terms of electrical activation, the electrical signals may bedirectly delivered to the electrode structure 282 as described withreference to FIG. 13, or indirectly delivered utilizing an inductor 286as illustrated in FIGS. 14-16 and 21. The embodiments of FIGS. 14-16 and21 utilize an inductor 286 which is operably connected to the driver 66of the control system 60 by way of electrical lead 284. The inductor 286comprises an electrical winding which creates a magnetic field 287 (asseen in FIG. 21) around the electrode structure 282. The magnetic field287 may be alternated by alternating the direction of current flowthrough the inductor 286. Accordingly, the inductor 286 may be utilizedto create current flow in the electrode structure 282 to thereby deliverelectrical signals to the vascular wall 40 to directly or indirectlyactivate the baroreceptors 30. In all embodiments, the inductor 286 maybe covered with an electrically insulative material to eliminate directelectrical stimulation of tissues surrounding the inductor 286. Apreferred embodiment of an inductively activated electrode structure 282is described in more detail with reference to FIGS. 21A-21C.

The embodiments of FIGS. 13-16 may be modified to form a cathode/anodearrangement. Specifically, the electrical inductor 286 would beconnected to the driver 66 as shown in FIGS. 14-16 and the electrodestructure 282 would be connected to the driver 66 as shown in FIG. 13.With this arrangement, the electrode structure 282 and the inductor 286may be any suitable geometry and need not be coiled for purposes ofinduction. The electrode structure 282 and the inductor 286 wouldcomprise a cathode/anode or anode/cathode pair. For example, whenactivated, the cathode 282 may generate a primary stream of electronswhich travel through the inter-electrode space (i.e., vascular tissueand baroreceptors 30) to the anode 286. The cathode is preferably cold,as opposed to thermionic, during electron emission. The electrons may beused to electrically or thermally activate the baroreceptors 30 asdiscussed previously.

The electrical inductor 286 is preferably disposed as close as possibleto the electrode structure 282. For example, the electrical inductor 286may be disposed adjacent the vascular wall as illustrated in FIG. 14.Alternatively, the inductor 286 may be disposed in an adjacent vessel289 as illustrated in FIG. 15. If the electrode structure 282 isdisposed in the carotid sinus 20, for example, the inductor 286 may bedisposed in the internal jugular vein 21 as illustrated in FIG. 15. Inthe embodiment of FIG. 15, the electrical inductor 286 may comprise asimilar structure as the electrode structure 282. As a furtheralternative, the electrical inductor 286 may be disposed outside thepatient's body, but as close as possible to the electrode structure 282.If the electrode structure 282 is disposed in the carotid sinus 20, forexample, the electrical inductor 286 may be disposed on the right orleft side of the neck of the patient as illustrated in FIG. 16. In theembodiment of FIG. 16, wherein the electrical inductor 286 is disposedoutside the patient's body, the control system 60 may also be disposedoutside the patient's body.

In terms of implant location, the electrode structure 282 may beintravascularly disposed as described with reference to FIG. 13, orextravascularly disposed as described with reference to FIG. 17, whichshow schematic illustrations of a baroreceptor activation device 300 inthe form of an extravascular electrically conductive structure orelectrode 302. Except as described herein, the extravascular electrodestructure 302 is the same in design, function, and use as theintravascular electrode structure 282. The electrode structure 302 maycomprise a coil, braid or other structure capable of surrounding thevascular wall. Alternatively, the electrode structure 302 may compriseone or more electrode patches distributed around the outside surface ofthe vascular wall. Because the electrode structure 302 is disposed onthe outside surface of the vascular wall, intravascular deliverytechniques may not be practical, but minimally invasive surgicaltechniques will suffice. The extravascular electrode structure 302 mayreceive electrical signals directly from the driver 66 of the controlsystem 60 by way of electrical lead 304, or indirectly by utilizing aninductor (not shown) as described with reference to FIGS. 14-16.

Refer now to FIG. 19 which shows a baroreceptor activation device 320 inthe form of electrically conductive particles 322 disposed in thevascular wall. This embodiment is substantially the same as theembodiments described with reference to FIGS. 13-18, except that theelectrically conductive particles 322 are disposed within the vascularwall, as opposed to the electrically conductive structures 282/302 whichare disposed on either side of the vascular wall. In addition, thisembodiment is similar to the embodiment described with reference to FIG.10, except that the electrically conductive particles 322 are notnecessarily magnetic as with magnetic particles 222, and theelectrically conductive particles 322 are driven by an electromagneticfiled rather than by a magnetic field.

In this embodiment, the driver 66 of the control system 60 comprises anelectromagnetic transmitter such as an radiofrequency or microwavetransmitter. Electromagnetic radiation is created by the transmitter 66which is operably coupled to an antenna 324 by way of electrical lead326. Electromagnetic waves are emitted by the antenna 324 and receivedby the electrically conductive particles 322 disposed in the vascularwall 40. Electromagnetic energy creates oscillating current flow withinthe electrically conductive particles 322, and depending on theintensity of the electromagnetic radiation and the resistivity of theconductive particles 322, may cause the electrical particles 322 togenerate heat. The electrical or thermal energy generated by theelectrically conductive particles 322 may directly activate thebaroreceptors 30, or indirectly activate the baroreceptors 30 by way ofthe surrounding vascular wall tissue.

The electromagnetic radiation transmitter 66 and antenna 324 may bedisposed in the patient's body, with the antenna 324 disposed adjacentto the conductive particles in the vascular wall 40 as illustrated inFIG. 19. Alternatively, the antenna 324 may be disposed in any of thepositions described with reference to the electrical inductor shown inFIGS. 14-16. It is also contemplated that the electromagnetic radiationtransmitter 66 and antenna 324 may be utilized in combination with theintravascular and extravascular electrically conductive structures282/302 described with reference to FIGS. 13-18 to generate thermalenergy on either side of the vascular wall.

As an alternative, the electromagnetic radiation transmitter 66 andantenna 324 may be used without the electrically conductive particles322. Specifically, the electromagnetic radiation transmitter 66 andantenna 324 may be used to deliver electromagnetic radiation (e.g., RF,microwave) directly to the baroreceptors 30 or the tissue adjacentthereto to cause localized heating, thereby thermally inducing abaroreceptor 30 signal.

Refer now to FIG. 20 which shows a baroreceptor activation device 340 inthe form of a Peltier effect device 342. The Peltier effect device 342may be extravascularly positioned as illustrated, or may beintravascularly positioned similar to an intravascular stent or filter.The Peltier effect device 342 is operably connected to the driver 66 ofthe control system 60 by way of electrical lead 344. The Peltier effectdevice 342 includes two dissimilar metals or semiconductors 343/345separated by a thermal transfer junction 347. In this particularembodiment, the driver 66 comprises a power source which deliverselectrical energy to the dissimilar metals or semiconductors 343/345 tocreate current flow across the thermal junction 347.

When current is delivered in an appropriate direction, a cooling effectis created at the thermal junction 347. There is also a heating effectcreated at the junction between the individual leads 344 connected tothe dissimilar metals or semiconductors 343/345. This heating effect,which is proportional to the cooling effect, may be utilized to activatethe baroreceptors 30 by positioning the junction between the electricalleads 344 and the dissimilar metals or semiconductors 343/345 adjacentto the vascular wall 40.

Refer now to FIGS. 21A-21C which show schematic illustrations of apreferred embodiment of an inductively activated electrode structure 282for use with the embodiments described with reference to FIGS. 14-16. Inthis embodiment, current flow in the electrode structure 282 is inducedby a magnetic field 287 created by an inductor 286 which is operablycoupled to the driver 66 of the control system 60 by way of electricalcable 284. The electrode structure 282 preferably comprises amulti-filar self-expanding braid structure including a plurality ofindividual members 282 a, 282 b, 282 c and 282 d. However, the electrodestructure 282 may simply comprise a single coil for purposes of thisembodiment.

Each of the individual coil members 282 a-282 d comprising the electrodestructure 282 consists of a plurality of individual coil turns 281connected end to end as illustrated in FIGS. 21B and 21C. FIG. 21C is adetailed view of the connection between adjacent coil turns 281 as shownin FIG. 21B. Each coil turn 281 comprises electrically isolated wires orreceivers in which a current flow is established when a changingmagnetic field 287 is created by the inductor 286. The inductor 286 ispreferably covered with an electrically insulative material to eliminatedirect electrical stimulation of tissues surrounding the inductor 286.Current flow through each coil turn 281 results in a potential drop 288between each end of the coil turn 281. With a potential drop defined ateach junction between adjacent coil turns 281, a localized current flowcell is created in the vessel wall adjacent each junction. Thus an arrayor plurality of bipoles are created by the electrode structure 282 anduniformly distributed around the vessel wall. Each coil turn 281comprises an electrically conductive wire material 290 surrounded by anelectrically insulative material 292. The ends of each coil turn 281 areconnected by an electrically insulated material 294 such that each coilturn 281 remains electrically isolated. The insulative material 294mechanically joins but electrically isolates adjacent coil turns 281such that each turn 281 responds with a similar potential drop 288 whencurrent flow is induced by the changing magnetic field 287 of theinductor 286. An exposed portion 296 is provided at each end of eachcoil turn 281 to facilitate contact with the vascular wall tissue. Eachexposed portion 296 comprises an isolated electrode in contact with thevessel wall. The changing magnetic field 287 of the inductor 286 causesa potential drop in each coil turn 281 thereby creating small currentflow cells in the vessel wall corresponding to adjacent exposed regions296. The creation of multiple small current cells along the inner wallof the blood vessel serves to create a cylindrical zone of relativelyhigh current density such that the baroreceptors 30 are activated.However, the cylindrical current density field quickly reduces to anegligible current density near the outer wall of the vascular wall,which serves to limit extraneous current leakage to minimize oreliminate unwanted activation of extravascular tissues and structuressuch as nerves or muscles.

To address low blood pressure and other conditions requiring bloodpressure augmentation, some of the baroreceptor activation devicesdescribed previously may be used to selectively and controllablyregulate blood pressure by inhibiting or dampening baroreceptor signals.By selectively and controllably inhibiting or dampening baroreceptorsignals, the present invention reduces conditions associated with lowblood pressure as described previously. Specifically, the presentinvention would function to increase the blood pressure and level ofsympathetic nervous system activation by inhibiting or dampening theactivation of baroreceptors.

This may be accomplished by utilizing mechanical, thermal, electricaland chemical or biological means. Mechanical means may be triggered offthe pressure pulse of the heart to mechanically limit deformation of thearterial wall. For example, either of the external compression devices120/160 described previously may be used to limit deformation of thearterial wall. Alternatively, the external compression device may simplylimit diametrical expansion of the vascular wall adjacent thebaroreceptors without the need for a trigger or control signal.

Thermal means may be used to cool the baroreceptors 30 and adjacenttissue to reduce the responsiveness of the baroreceptors 30 and therebydampen baroreceptor signals. Specifically, the baroreceptor 30 signalsmay be dampened by either directly cooling the baroreceptors 30, toreduce their sensitivity, metabolic activity and function, or by coolingthe surrounding vascular wall tissue thereby causing the wall to becomeless responsive to increases in blood pressure. An example of thisapproach is to use the cooling effect of the Peltier device 340.Specifically, the thermal transfer junction 347 may be positionedadjacent the vascular wall to provide a cooling effect. The coolingeffect may be used to dampen signals generated by the baroreceptors 30.Another example of this approach is to use the fluid delivery device 260to deliver a cool or cold fluid (e.g. saline). In this embodiment, thedriver 66 would include a heat exchanger to cool the fluid and thecontrol system 60 may be used to regulate the temperature of the fluid,thereby regulating the degree of baroreceptor 30 signal dampening.

Electrical means may be used to inhibit baroreceptor 30 activation by,for example, hyperpolarizing cells in or adjacent to the baroreceptors30. Examples of devices and method of hyperpolarizing cells aredisclosed in U.S. Pat. No. 5,814,079 to Kieval, and U.S. Pat. No.5,800,464 to Kieval, the entire disclosures of which are herebyincorporated by reference. Such electrical means may be implementedusing any of the embodiments discussed with reference to FIGS. 13-18 and21.

Chemical or biological means may be used to reduce the sensitivity ofthe baroreceptors 30. For example, a substance that reduces baroreceptorsensitivity may be delivered using the fluid delivery device 260described previously. The desensitizing agent may comprise, for example,tetrodotoxin or other inhibitor of excitable tissues. From theforegoing, it should be apparent to those skilled in the art that thepresent invention provides a number of devices, systems and methods bywhich the blood pressure, nervous system activity, and neurohormonalactivity may be selectively and controllably regulated by activatingbaroreceptors or by inhibiting/dampening baroreceptor signals. Thus, thepresent invention may be used to increase or decrease blood pressure,sympathetic nervous system activity and neurohormonal activity, asneeded to minimize deleterious effects on the heart, vasculature andother organs and tissues.

The baroreceptor activation devices described previously may also beused to provide antiarrhythmic effects. It is well known that thesusceptibility of the myocardium to the development of conductiondisturbances and malignant cardiac arrhythmias is influenced by thebalance between sympathetic and parasympathetic nervous systemstimulation to the heart. That is, heightened sympathetic nervous systemactivation, coupled with decreased parasympathetic stimulation,increases the irritability of the myocardium and likelihood of anarrhythmia. Thus, by decreasing the level of sympathetic nervous systemactivation and enhancing the level of parasympathetic activation, thedevices, systems and methods of the current invention may be used toprovide a protective effect against the development of cardiacconduction disturbances.

EXPERIMENTAL

An electrode system was introduced into the inferior vena cava of ananesthetized dog. The electrode system was an eight lead, 64-electrode8F Constellation® catheter from Boston Scientific EP Technologies,Sunnyvale, Calif. The electrode system was placed endovascularly in theabdominal vena cava. The electrode system was activated using trains ofelectrical impulses of 0-6 volts, a frequency of 100 hz, and a pulsewidth of 0.5 ms. During various activation experiments, arterialpressure, mean arterial pressure and heart rate were monitored. Theresults of three experiments are shown in FIGS. 22A-C. These figuresdemonstrate a change in blood pressure as energy is applied to thevessel wall, with recovery to pre-activation levels when the energy isdiscontinued.

Those skilled in the art will recognize that the present invention maybe manifested in a variety of forms other than the specific embodimentsdescribed and contemplated herein. Accordingly, departures in form anddetail may be made without departing from the scope and spirit of thepresent invention as described in the appended claims.

1. An apparatus comprising: at least one fixation electrode adapted toabut a wall of a pulmonary artery; a pressure sensor integrallysupported by the at least one fixation electrode, the pressure sensorproviding a signal indicative of a blood pressure in the pulmonaryartery; a pulse generator coupled with the at least one fixationelectrode, the pulse generator adapted to deliver a baroreflexstimulation signal to one or more baroreceptors in the pulmonary arteryvia the at least one fixation electrode; and wherein the pressure sensoris anchorable in the pulmonary artery via the at least one fixationelectrode.
 2. The apparatus as recited in claim 1, wherein the at leastone fixation electrode is expandable to fix the electrode and thepressure sensor in place by frictional forces.
 3. The apparatus asrecited in claim 1, wherein the at least one fixation electrodecomprises, at least in part, an electrically insulated surface.
 4. Theapparatus as recited in claim 1, further comprising a second sensoradapted to sense a physiological parameter.
 5. The apparatus as recitedin claim 1, further comprising a posture sensor adapted to sense aposture signal, the posture signal for use in normalizing the signalindicative of the blood pressure in the pulmonary artery.
 6. Theapparatus as recited in claim 1, further comprising a controller coupledwith one or both of the pressure sensor or the pulse generator, thecontroller adapted to control the baroreflex stimulation signal orreceive the signal indicative of the pulmonary artery blood pressure. 7.The apparatus as recited in claim 6, further comprising an implantablemedical device, the implantable medical device including the pulsegenerator, the controller, and an apparatus power source.
 8. Theapparatus as recited in claim 7, wherein the pressure sensorintermittently or continuously provides the signal indicative of thepulmonary artery blood pressure to the implantable medical device. 9.The apparatus as recited in claim 7, further comprising a lead bodyextending from a lead proximal end to a lead distal end, the lead bodyconnecting the implantable medical device and the at least one fixationelectrode; and wherein the at least one fixation electrode is couplednear the lead distal end.
 10. The apparatus as recited in claim 9,further comprising a second electrode coupled with the lead bodyproximally from the at least one fixation electrode.
 11. The apparatusas recited in claim 6, wherein the coupling between the controller andone or both of the pressure sensor or pulse generator includes at leastone wireless link.
 12. The apparatus as recited in claim 11, furthercomprising an external device including the controller; and wherein thepressure sensor provides the signal indicative of the pulmonary arteryblood pressure to the external device at a predetermined time intervalor in response to a user-generated command.
 13. The apparatus as recitedin claim 1, further comprising at least one apparatus power sourceadapted to provide power to the pressure sensor and the pulse generator.14. The apparatus as recited in claim 13, wherein the at least oneapparatus power source comprises a capacitor or a battery coupled withthe pressure sensor, the capacitor chargeable by an external charger.15. The apparatus as recited in claim 13, wherein the at least oneapparatus power source comprises a battery coupled with the pressuresensor.
 16. An apparatus comprising: an expandable electrode having anexpanded diameter dimensioned to abut a wall of a pulmonary artery; apulmonary artery pressure sensor coupled to the expandable electrode,the pressure sensor adapted to monitor blood pressure in the pulmonaryartery; a pulse generator electrically coupled with the expandableelectrode, the pulse generator being adapted to deliver a baroreflexstimulation signal to a baroreceptors in the pulmonary artery by way ofthe expandable electrode; and wherein the expandable electrode isadapted to fix the pulmonary artery pressure sensor in place byfrictional forces.
 17. The apparatus as recited in claim 16, wherein theexpandable electrode includes an expandable stent structure adapted tobe intravascularly delivered in a collapsed state and expanded whenpositioned in the pulmonary artery.
 18. The apparatus as recited inclaim 16, wherein the pulse generator is further adapted to generate acardiac pacing signal; and wherein the apparatus includes a secondelectrode positioned to deliver the cardiac pacing signal to capture aheart.
 19. A method comprising: forming an expandable electrode,including forming an expanded shape dimensioned to abut a wall of apulmonary artery; securing a pulmonary artery pressure sensor to theexpandable electrode such that the pressure sensor is fixable in thepulmonary artery via the expandable electrode; and wherein theexpandable electrode and the pulmonary artery pressure sensor areadapted to be fed through a right ventricle and a pulmonary valve intothe pulmonary artery.
 20. The method as recited in claim 19, furthercomprising forming a pulse generator, including programming the pulsegenerator to deliver a baroreflex stimulation signal to a baroreceptorsin the pulmonary artery via the expandable electrode; and coupling thepulse generator with the expandable electrode.
 21. A method of usecomprising: implanting an expandable electrode having an integratedpressure sensor within a pulmonary artery such that an outer surface ofthe electrode abuts a wall of the pulmonary artery; monitoring a signalindicative of a blood pressure in the pulmonary artery using thepressure sensor; and delivering a baroreflex stimulation signal to oneor more baroreceptors in the pulmonary artery via the electrode.
 22. Themethod as recited in claim 21, further comprising comparing the signalindicative of the pulmonary artery blood pressure with a predeterminedpressure signal threshold.
 23. The method as recited in claim 22,wherein delivering the baroreflex stimulation includes using thecomparison between the signal indicative of the pulmonary artery bloodpressure and the predetermined pressure signal threshold.
 24. The methodas recited in claim 21, wherein implanting includes feeding theexpandable electrode integrated with the pressure sensor through a rightventricle and a pulmonary valve into the pulmonary artery to positionthe electrode and sensor.
 25. The method as recited in claim 21, furthercomprising modifying the baroreflex stimulation signal using the signalindicative of the blood pressure in the pulmonary artery.
 26. The methodas recited in claim 21, further comprising monitoring a signalindicative of a then-current posture; and normalizing the signalindicative of the blood pressure in the pulmonary artery using thesignal indicative of the then-current posture.